Delivery device

ABSTRACT

A delivery device, e.g. an inhaler, comprises a rotatable metering member adapted to dispense a measured amount of material, a material delivery passage and a material delivery orifice and at least one actuator member adapted to move the metering member from a material retaining position to a material dispensing position. In a magazine comprising a plurality of metering members, the actuator and metering members may operate in a radial direction. A plurality of rotatable magazines may be utilized in the delivery device. The delivery device may be used to deliver a single or a combination therapy.

The present application is a continuation of U.S. patent applicationSer. No. 11/680,984, which is a division of U.S. patent application Ser.No. 10/070,146, now U.S. Pat. No. 7,219,665, issued May 22, 2007, whichis a U.S. national phase application based on PCT InternationalApplication No. PCT/GB00/03377, filed Sep. 4, 2000, which claimspriority from British Patent Application No. GB 9920839.9, filed Sep. 4,1999, all of which are hereby incorporated by reference in theirentirety.

FIELD OF INVENTION

This invention relates to a novel form of material delivery device, forexample, a medicament delivery device, such as an inhaler. In particularthe invention provides a novel form of dry powder inhaler and a methodof delivering a medicament.

BACKGROUND OF THE INVENTION

Dry powder inhalers are known, such as TECHNOHALER, being developed byInnovata Biomed in the UK. Such a device is described in InternationalPatent Application No. WO 93/16748 (PCT/GB93/00335). WO '748 describesan inhaler which comprises a disc like magazine having a plurality ofmedicament carrying receptacles around its periphery. Each receptaclecomprises a spool housed in a spool carrier. Each spool has a flange ateach end which form a tight slidable fit within the body of the spoolcarrier. The space left between the body of the spool and the spoolcarrier is filled with an appropriate medicament.

The known TECHNOHALER is provided with suitable indexing means,including a push button and a ratchet mechanism which engages with theupper surface of the disc. Depression of the push button urges a pushrod to push the spool, which is adjacent the inhalation passage of theinhaler, downwards and almost fully out of the spool carrier, and intothe inhalation passage. As the spool is pushed into the inhalationpassage, it carries with it the measured quantity of medicament which ithas been used to contain inside the magazine. The user can then inhalethrough the mouthpiece so as to take up the drug now released into theinhalation passage. The upper flange of the spool remains, however, heldby the lower part of the receptacle. When the user then releases pushbutton, the ratchet mechanism causes the disc to rotate by one step sothat the next receptacle is brought into register with the inhalationpassage. The inhaler is thus reset and ready for delivery of anotherdose of drug. The “empty” spool not having been pushed fully out of thefirst receptacle, continues to move round with the first receptacle,supported by the lower guide.

In the inhaler of the prior art whilst the spool magazine liesessentially in the same plane as the as the mouthpiece of the inhaler,the push rod acts on a spool in a perpendicular plane.

BRIEF SUMMARY OF THE INVENTION

We have now found a novel form of medicament delivery device in which apush rod lies in essentially the same plane as the delivery orifice ofthe device and actuates the spool in a direction which is coaxial withthe delivery orifice of the device. Thus when a plurality of spools arearranged radially in a magazine, such that the longitudinal axis of thespools lie in the same plane as the magazine and the spool may beexpressed radially from the magazine. This has the advantage that, interalia, a significantly slimmer device may be produced. Furthermore, theradial expression of the spools means that more than one magazine can beplaced in the device and thus, inter alia, the device may deliver higherdosages, combination therapies and/or provide medication over a longerperiod of time.

Thus, according to the invention we provide a delivery device comprisinga rotatable metering member adapted to dispense a measured amount ofmaterial, a material delivery passage and a material delivery orifice,and at least one actuator member adapted to move the metering memberfrom a material retaining position to a material dispensing positioncharacterised in that the actuator member moves in a substantiallyradial direction and actuates the metering member in a substantiallyradial direction.

The device of the invention has utility in a variety of areas,including, for example, medicament delivery. Thus, it is especiallysuited as an inhaler and especially a dry power inhaler (DPI).

According to a preferred feature of the invention the device is providedwith a plurality of metering members housed in a magazine, preferably asubstantially circular magazine. In an especially preferred embodiment aplurality of magazines may be loaded into the delivery device of theinvention, e.g. a pair of magazines.

When the metering member is in the medicament retaining position it ispreferably out of communication with the inhalation passage and whilstthe metering member is in the medicament dispensing position it ispreferably in communication with the inhalation passage.

The metering member is of such dimensions as to be able to pass into theinhalation passage. The metering member may comprise those described inWO 93/16748. Thus, in one embodiment the metering member may comprise aspool housed in a spool carrier. The spool carrier acts as a conduit forthe spool to communicate with the inhalation passage. Thus the spoolwill be provided with a flange at each end such that the flanges are insealing engagement with the inner walls of the conduit and a spaceexists between the inner walls of the conduit and the non-flangedportion of the spool. In the filled metering member, the space is takenup by a measured dosage of medicament. Indeed, the plug, flanges andconduit are so dimensioned so as to predetermine the amount ofmedicament available. In an alternative embodiment of the invention themetering member may comprise a medicament container with a closed endand an open end, a cap adapted to abut the open end of the container anda sleeve adapted to overlap the open end of the container and the cap.Reference hereinafter to a spool and spool carrier is intended toencompass a capped cartridge as hereinbefore described.

The spool and spool carrier is generally that described in the prior artpatent application. However, instead of the spool being mounted in avertical position each spool is essentially horizontally mounted. Forthe sake of clarity, the spools are positioned in the same plane as theplane of the disc magazine. The push rod used to eject the spool fromthe spool carrier therefore operates radially from the centre of thedisc and does not push the spool out of the disc plane.

The actuator member may comprise a push rod mechanism which may besubstantially similar to that known conventionally save that it actsradially.

Alternatively, when a plurality of magazines is used the actuator membermay, for example, comprise a pair of push rods.

As hereinbefore described a significant advantage of the device of theinvention is that it can be used to deliver combination therapies ifdesirable.

Increasingly, patients are required to take more than one medicine andthis is no less the case in the treatment of bronchial disorders. Thus,for example, combination therapies such as a steroid with a β₂ agonist,e.g. fluticasone and salmeterol, have been commercially successful. Todate, the administration of such combination therapies comprises the useof a predetermined formulation either as a dry powder, e.g. in a gelatincapsule or a foil blister; or alternatively as a metered dose aerosol.However, this approach suffers from the disadvantage, inter alia, thatthe medical practitioner is restricted in that it is not possible tovary the quantities of the two medicaments administered. Thus, there hastherefore been a long felt need for a dry powder inhalation system whichpermits the administration of combination therapies.

It is within the scope of this invention for more than two medicamentsto be administered, however, it is considered most likely that dualcombination therapies would be preferred by the medical profession. Thusthe description hereinafter will generally refer to an inhaler adaptedto administer a dual combination medicament, but it would be wellunderstood by one skilled in the art that these references could beconstrued to multiple combinations.

Thus according to a further feature of the invention we provide a drypowder inhaler as hereinbefore described characterised in that theinhaler is adapted to take a plurality of disc magazines. The medicamentencapsulated in the spool carriers of the two disc magazines may be thesame or different. In one embodiment the medicaments are different andthus the inhaler is used to deliver a combination therapy.Alternatively, the medicament encapsulated by the spool carrier mayitself be a combination therapy.

In a further embodiment of the invention a medicament delivery device,e.g. an inhaler, comprises a pair of disc magazines. Such a device maypreferentially be provided with means for engaging a first magazinewhilst disengaging a second magazine and which is moveable from anengaging to a disengaging position and vice-versa.

Such means may comprise male and female interlocking members.Preferentially, the disc magazine is provided with a female member and adrive means is provided with a male member.

In an especially preferred embodiment a drive plate is provided with amale member and is adapted to engage with the drive means.

The male member may comprise a resilient protrusion which is resilientlybiased towards a second disc magazine, but is constructed so as to beurged to engage with a female member of a first disc magazine, such thatwhen the urging means is removed the male member is biased towards andengages with the second magazine.

A variety of medicaments may be administered by using the inhaler of theinvention, such medicaments may have a systemic or non-systemic activityon the patient. Such medicaments are generally (but not limiting)antibiotics, bronchodilators or other anti-asthma drugs. Suchmedicaments include, but are not limited to β₂-agonists, e.g. fenoterol,formoterol, pirbuterol, reproterol, rimiterol, salbutamol, salmeteroland terbutaline; non-selective beta-stimulants such as isoprenaline;xanthine bronchodilators, e.g. theophylline, aminophylline and cholinetheophyllinate; anticholinergics, e.g. ipratropium bromide; mast cellstabilisers, e.g. sodium cromoglycate and ketotifen; bronchialanti-inflammatory agents, e.g. nedocromil sodium; and steroids, e.g.beclomethasone dipropionate, fluticasone, budesonide and flunisolide;and combinations thereof.

Specific combinations of medicaments which may be mentioned includecombinations of steroids, such as, beclomethasone dipropionate,fluticasone, budesonide and flunisolide; and combinations of twoβ₂-agonists, such as, formoterol and salmeterol. It is also within thescope of this invention to include combinations of one or more of theaforementioned steroids with one or more of the aforementionedβ₂-agonists.

Further medicaments which may be mentioned include systemically activematerials, such as, proteinaceous compounds and/or macromolecules, forexample, hormones and mediators, such as insulin, human growth hormone,leuprolide and alpha interferon; growth factors, anticoagulants,immunomodulators, cytokines and nucleic acids.

When dual disc magazines are used the inhaler will be provided with tworadially acting push rod mechanisms. These mechanisms may be adapted tooperate together, independently or sequentially.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be illustrated by way of example only and withreference to the accompanying drawings, in which:

FIG. 1 is a cross-sectional view of a spool and spool carrier;

FIG. 2 is a perspective view of a single disc magazine comprisingspools;

FIG. 3 is a schematic representation of the ejection of a spool from thespool carrier;

FIG. 4 is a perspective view of a combination therapy disc magazine;

FIG. 5 is a cross-sectional view of the combination therapy mechanism;

FIG. 6 is a perspective view of a disc magazine provided with an emptyspool holder;

FIG. 7 is a perspective view of a pair of disc magazines provided with adrive plate;

FIG. 8 is a schematic representation of a pair of magazines providedwith a drive plate;

FIG. 9 is a schematic representation of the carousel in operation withdual plunger rods;

FIG. 10 is a schematic representation of the device when the first(lower) carousel has completed a 360° rotation;

FIG. 11 is a perspective view of an alternative embodiment of a drivedisc;

FIG. 12 is a perspective view of a pair of disc magazines with a drivedisc;

FIG. 13 is a schematic representation of a device in operation with adual plunger rod; and

FIG. 14 is a schematic representation of a device when the first (lower)carousel has completed a 360° rotation.

DETAILED DESCRIPTION OF THE INVENTION

With reference to FIG. 1, a single medicament dose unit (1) is comprisedof a spool (2), a spool carrier (3) and a single dose of medicament (4),for use in a dry powder inhaler. The spool (2) comprises a longitudinalbody (5) and terminal flanges (6 and 7) at each end. The sides (8 and 9)of the flanges (6 and 7) form a seal and a tight slidable fit with theinner walls (10 and 11) of the spool carrier (3). The length of thespool (2) and the length of the spool carrier (3) are substantially thesame. Each flange is provided with an external face (12 and 13).

With reference to FIGS. 2 and 3, a plurality of spools (2) and carriers(3) are joined in a disc to form a magazine. The plurality of dose units(1) arranged radially around the circumference of the magazine (14). Theinhalation device is provided with a dispensing mechanism (not shown)and a push rod (15) which also acts radially. The push rod (15) whenactuated operates in the radial plane of the magazine (14) ejecting aspool (2) radially from the spool carrier (3) into the inhalationpassage (not shown). The spool (2) remains in the plane of the magazine(14) and the flange (7) remains in co-operation with the spool carrier(3) so that it can move out of the inhalation passage upon rotation ofthe magazine (14).

With reference to FIGS. 4 and 5, a “double decker” arrangement isachieved by joining a first magazine (14) with a second magazine (16).The inhaler mechanism is provided with a first push rod (5) and a secondpush rod (17). The push rods may be actuated jointly, separately orsequentially optionally allowing medicament to be dispensed at the sametime in the spool from the first magazine (14) as in the spool from thesecond magazine (16).

With reference to FIG. 6, a spool carrier magazine (101) comprises adisc provided with a plurality of radially mounted spool carriers (102).Each of the spool carriers (102) (save for one) is provided with a spool(103). One of the spool carriers (104) is empty and is provided with acut away portion (105).

With reference to FIG. 7, a pair of spool carrier magazines (101 a and101 b) are provided. A drive disc (106) comprises a substantially planarannular disc. The inner surface (107) of the drive disc (106) isprovided with a plurality of teeth (108) which are adapted to engagewith a drive means (not shown).

Adjacent to the periphery (109) of the drive disc (106), the disc isprovided with an aperture (110) through which protrudes an out of planeresilient male member (111). The male member (111) is biased towards oneof the magazines. By way of example only, the embodiment described isone in which the male member (111) is biased towards the uppermostmagazine (101 b), although it should be understood that the presentapplication should be read to also encompass an embodiment in which themale member may be biased towards the other magazine (101 a).

The drive disc (106) is positioned adjacent to the first magazine (101b) such that the male member (111) overlies the cut away portion (105)and the empty spool carrier (104). When the second magazine (101 a) ispositioned in place it is arranged such that a filled spool carrier(102) overlies the male member (111). The circumferential surface restsagainst the male member (111) and urges it into an engaging positionwith the empty spool carrier (104).

Thus, in use, when the annular drive disc (106) is rotated, the malemember (111) engages with the empty spool carrier (104) to rotate thefirst magazine (101 b) whilst the second magazine (101 a) is disengagedand therefore remains unmoved.

With reference to FIGS. 8-10, the assembly of the system is illustrated.Thus, the assembly (113) comprises a chassis (114) and the drive disc(106) is placed above the magazine (101 b). The male member (111) isbiased away from the magazine (101 b) and therefore protrudes above theplane of the drive disc (106). The second upper magazine (101 a) is thenpositioned above the drive disc (106).

The male member (111) comprises a substantially triangular shaped tabwith a first surface (117), a second surface (116), a hinged end (118)and a distal end. Optionally, the hinged end (118) may be provided witha groove (119) to facilitate the flexible movement of the male member(111). In its free position the male member (111) rests such that thefirst surface (117) lies in the plane of the drive disc (106) and thesecond surface (116) lies out of the plane and protrudes from the drivedisc (106).

When the second, upper magazine (101 a) is in place, the lower, outersurface of the spool carrier magazine is urged against the secondsurface (116) of the male member (111). This urges the second surface(116) to lie in the plane of the drive disc (106) and therefore thefirst surface (117) lies out of the plane, enabling it to engage withthe empty spool carrier (104).

A push rod (121) is also provided which comprises a pair of spoolprodders (122 a and 122 b). The push rod (121) is connected to anactuator means (not shown). A chassis lid (114 a) is provided to closethe system.

With reference to FIGS. 11 to 14, a further embodiment is illustrated inwhich the male member (111 a) protrudes beyond the peripheral edge (123)of the drive disc (106). The chassis (114 a) is provided with two setsof guide rails (124 and 125). The device is assembled so that the malemember (111 a) is tensioned and the peripheral end (126) of the malemember (111 a) held in the guide rail (125). When the lower magazine hasrotated through approximately 360°, the male member (111 a) reaches abreak in the guide rails (124 and 125), thus allowing the male member(111 a) to be urged towards the second magazine and into the secondguide rail (124).

1-21. (canceled)
 22. A delivery device comprising a first rotatablemagazine and a second rotatable magazine, each magazine being providedwith a plurality of metering members adapted to dispense a measuredamount of material, a first push rod adapted to move a metering memberof the first rotatable magazine from a material retaining position to amaterial dispensing position, a second push rod adapted to move ametering member of the second rotatable magazine from a materialretaining position to a material dispensing position, a materialdelivery passage, and a material delivery orifice.
 23. A delivery deviceas claimed in claim 22, wherein the first and second push rods areadapted to operate together.
 24. A delivery device as claimed in claim22, wherein the first and second push rods are adapted to operateindependently.
 25. A delivery device as claimed in claim 22, wherein thefirst and second push rods are adapted to operate sequentially.
 26. Adelivery device according to claim 22, wherein the material is a drypowder.
 27. A delivery device as claimed in claim 22, wherein thematerial comprises a medicament.
 28. A delivery device according toclaim 27, wherein the medicament delivery device is an inhaler.
 29. Adelivery device according to claim 27, wherein the first and secondmagazines contain the same medicament.
 30. A delivery device accordingto claim 27, wherein the first and second magazines contain differentmedicaments.
 31. A delivery device as claimed in claim 27, wherein thefirst and second magazines each contain a material that comprises acombination therapy.
 32. A delivery device as claimed in claim 31,wherein the combination therapy comprises fluticasone and salmeterol.33. A method of delivering a material which comprises using a deliverydevice according to claim
 22. 34. A method of administering a medicamentusing an inhaler according to claim
 28. 35. A method according to claim34 characterised in that a combination of medicaments are administered.36. A method of treatment of a patient suffering from a respiratorydisorder comprising the administration of a therapeutically effectiveamount of a medicament using an inhaler according to claim 28.